The present invention relates to a non-invasive method and apparatus for pre selecting the drug delivery profile of a drug by controlling the concentration of ions added to or present in the reservoir containing the drug to be delivered, which ions would compete with the drug ions for the current.
Iontophoretic drug delivery systems, have, in recent years, become an increasingly important means of administering drugs.
Presently there are two types of transdermal drug delivery systems, i.e., passive and iontophoretic. Passive patch systems deliver small and relatively lipophilic drugs through the skin of the patient by diffusion, an example of which would involve the application of the Duragesic(copyright) patch which releases the narcotic analgesic, fentanyl, to provide pain relief Iontophoresis systems, on the other hand, deliver drug through the skin of the patient through the application of an electromotive force (iontophoresis) to drive ionizable substances (medicament/drug) into the skin so that they can be absorbed by adjacent tissues and blood vessels. Iontophoresis, therefore, allows charged and hydrophilic drugs to be transported across the skin which are poorly deliverable through passive diffusion. Transdermal systems offer advantages clearly not achievable by other modes of administration, such as hypodermic injection which has the associated problem of pain, risk of infection and trauma to the patient Iontophoresis also has advantages over oral administration in that continuous and prolonged delivery can be achieved. In addition inactivation of the medicament, food interactions, first pass hepatic metabolism and gastrointestinal side effects may be avoided.
Conventional iontophoretic devices, such as those described in U.S. Pat. Nos. 4,820,263 (Spevak, et al.), 4,927,408 (Haak, et al.) and 5,084,008 (Phipps), the disclosures of which are hereby incorporated by reference, provide for delivery of a drug or medicament transdernally through iontophoresis. Basically, conventional iontophoretic devices consist of a power source connected to two electrodes, an anode and a cathode, which are individually in ionic contact with an electrolyte or drug reservoir which is in contact with the skin to be treated by the iontophoretic device. When the current is turned on, electrical energy is used to assist in the transport of ionic molecules into the body through the skin, via ionic conduction.
In general, the flux of a drug across the skin from an iontophoretic device is proportional to current, thus, a way to obtain varied flux or drug delivery profiles would be to vary the current. By way of example, if one wanted to administer a bolus-like (or peaked) flux, one would need to increase the current at first and then decrease the current after the bolus has been achieved. However, to vary the current adds complexities to the iontophoresis control circuit and it also increases the likelihood that the patient will feel sensation due to the changes in the current being administered.
The method and apparatus of the present invention overcomes these shortcomings and provides a method and apparatus for pre-selecting or controlling the drug delivery of flux profile of a drug being iontophoretically delivered.
One embodiment of the present invention provides a method for controlling the flux profile of drug delivered by iontophoresis by, prior to ionthophoretic delivery adding to or having present in the reservoir containing the drug, ions which would compete with the drug ions for current (hereinafter referred to as xe2x80x9ccompeting ionsxe2x80x9d). To achieve various flux profiles for the drug being delivered, one may use constant current, thus avoiding the shortcomings of prior methods, but vary the concentration of the competing ions.
Another embodiment of the present invention provides for an iontophoretic device for controlling the flux profile of drug delivered by iontophoresis by, prior to iontophoretic delivery, adding to or having present in the reservoir containing the drug, ions which would compete with the drug ions for current. The iontophoretic device has
(a) a current distributing member;
(b) an ionized substance reservoir containing an ionized or ionizable substance, in electrical communication with the current distributing member and adapted to be placed in ionic communication with the epithelial surface of a subject;
(c) an electrolyte reservoir containing an electrolyte, in electrical communication with an indifference electrode and in ionic communication with an epithelial surface; and
(d) an electrical power source in current delivering connection with the current distribution member and the electrolyte reservoir.